Mast Cell-mediated Allergic Reactions Research Articles

Anti-Allergic Effects of Artemisia iwayomogi on Mast Cell-Mediated Allergy Model

The discovery of drugs for the treatment of allergic disease is an important subject in human health. The Artemisia iwayomogi (Compositae) (AIE) has been used as a traditional medicine in Korea and is known to have an anti-inflammatory effect. However, its specific mechanism of action is still unknown. In this report, we investigated the effect of AIE on the mast cell-mediated allergy model and studied the possible mechanism of action. AIE inhibited compound 48/80-induced systemic reactions and plasma histamine release in mice. AIE decreased immunoglobulin E (IgE)-mediated local allergic reaction, passive cutaneous anaphylaxis (PCA) reaction. AIE dose dependently attenuated histamine release from rat peritoneal mast cells activated by compound 48/80 or IgE. AIE decreased the compound 48/80-induced intracellular Ca(2+). Furthermore, AIE decreased the phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187-stimulated tumor necrosis factor-alpha and interleukin-6 gene expression and production in human mast cells. The inhibitory effect of AIE on the proinflammatory cytokine was p38 mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF-kappaB) dependent. AIE attenuated PMA plus A23187-induced degradation of IkappaBalpha and nuclear translocation of NF-kappaB and specifically blocked activation of p38 MAPK but not that of c-jun N-terminal kinase and extracellular signal-regulated kinase. Our findings provide evidence that AIE inhibits mast cell-derived immediate-type allergic reactions and involvement of intracellular Ca(2+), proinflammatory cytokines, p38 MAPK, and NF-kappaB in these effects.

Inhibitory activity of Chrysanthemi sibirici herba extract on RBL-2H3 mast cells and compound 48/80-induced anaphylaxis

The effects of extracts from various oriental medicinal herbs on mast cell-mediated allergic reaction were investigated. Among them, Chrysanthemi sibirici herba ethanol extract exerted the potent inhibitory activity on antigen-induced degranulation in RBL-2H3 mast cells. Chrysanthemi sibirici herba dose-dependently inhibited DNP–BSA or compound 48/80-induced degranulation in RBL-2H3 mast cells, with IC 50 values of approximately 49 μg/ml and 76 μg/ml, respectively. This extract strongly suppressed compound 48/80-induced systemic anaphylaxis by 48.7% at a dose of 300 mg/kg in mice. Chrysanthemi sibirici herba also inhibited the expression of TNF-α and the activation of the MAP kinase, ERK1/2, which is critical for the production of inflammatory cytokines in mast cells, as indicated by the suppression of activating phosphorylation of ERK1/2. These results lead us to conclude that Chrysanthemi sibirici herba may be used clinically to treat various allergic diseases.

In-vitro and in-vivo anti-allergic actions of Arecae semen.

The effects of various extracts from oriental medicinal herbs on mast cell-mediated allergic reactions have been investigated. Among the extracts, Arecae semen was the most potent inhibitor of antigen-induced degranulation in RBL-2H3 mast cells. A. semen inhibited DNP-BSA- and compound 48/80-induced degranulation in RBL-2H3 mast cells with IC(50) values of approximately 53 and 52 microg mL(-1), respectively, and inhibited compound 48/80-induced systemic anaphylaxis by 46% at 300 mg kg(-1) in mice. A. semen also inhibited the expression of TNF-alpha and the activation of mitogen activated protein kinase, ERK1/2, which is critical for the production of inflammatory cytokines in mast cells, as indicated by the suppression of the activating phosphorylation of ERK1/2. These results suggest that A. semen may be useful for the treatment of various immediate and delayed allergic diseases.

Effect of disodium cromoglycate on mast cell-mediated immediate-type allergic reactions

We investigated the effect of disodium cromoglycate (DSCG) on mast cell-mediated immediate-type hypersensitivity. DSCG inhibited systemic allergic reaction induced by compound 48/80 dose-dependently. Passive cutaneous anaphylaxis was inhibited by 71.6% by oral administration of DSCG (1 g/kg). When DSCG was pretreated at concentration rang from 0.01–1000 g/kg, the serum histamine levels were reduced in a dose dependent manner. DSCG also significantly inhibited histamine release from rat peritoneal mast cell (RPMC) by compound 48/80. We confirmed that DSCG inhibited compound 48/80-induced degranulation of RPMC by alcian blue/nuclear fast red staining. In addition, DSCG showed a significant inhibitory effect on anti-dinitrophenyl IgE-mediated tumor necrosis factor-α production. These results indicate that DSCG inhibits mast cell-mediated immediate-type allergic reaction.

Inhibition of mast cell-dependent immediate-type hypersensitivity reactions by purple bamboo salt

Purple bamboo salt is a specially processed salt according to the traditional recipe using normal salt and bamboo etc. It has been used as a folk medicine for the purpose of prevention and treatment of various diseases in Korea. This report describes an inhibitory effect of purple bamboo salt on mast cell-mediated immediate-type allergic reactions. Purple bamboo salt (0.01–1 μg per site) significantly inhibited the ear swelling response induced by intradermal injection of compound 48/80 in mice. Purple bamboo salt (0.01–1 mg/ml) dose-dependently inhibited the histamine release from the rat peritoneal mast cells (RPMCs) by compound 48/80. Purple bamboo salt (0.01–1 g/kg) also dose-dependently inhibited the passive cutaneous anaphylaxis (PCA) by oral administration. Our results provide evidence that purple bamboo salt will be beneficial in the regulation of immediate-type of allergic reactions.

Inhibitory effects of Xanthii fructus extract on mast cell-mediated allergic reaction in murine model

The effect of aqueous extract of Xanthii fructus (XF) on mast cell-mediated allergic reaction has been investigated. XF inhibited compound 48/80-induced systemic anaphylaxis in mouse. This dose-dependently inhibited histamine release from rat peritoneal mast cells (RPMC) by compound 48/80. Additionally, XF inhibited local immunoglobulin E (IgE)-mediated passive cutaneous anaphylatic reaction. When XF (0.1 mg/ml) was added, the secretion of tumor necrosis factor-α (TNF-α) from anti-dinitrophenyl (DNP) IgE antibody-stimulated mast cells was inhibited by 56%. Our studies provide evidence that XF may be beneficial in the treatment of various types allergic diseases.

INHIBITORY EFFECT OF MAST CELL-MEDIATED ACUTE AND CHRONIC ALLERGIC REACTIONS BY DODUTANG

ABSTRACTDodutang has been used for treatment of various allergic inflammation diseases in Korea. However, it is still unclear how Dodutang prevents these diseases in experimental animal models. Mast cells play an important roles in allergic and other inflammatory reactions by producing a spectrum of powerful mediators including preformed and de novo synthesized cytokines. In this study, we investigated the effect of Dodutang on mast cell-mediated allergic and inflammatory reactions. Dodutang (0.001–5 g/L) significantly inhibited the histamine release from rat peritoneal mast cells activated by compound 48/80. Dodutang (0.001–5 g/kg) dose-dependantly inhibited the passive cutaneous anaphylaxis reaction activated by anti-dinitrophenyl (DNP) IgE in a rat model, especially, by 78.96% at the concentration of 5 g/kg. In addition, Dodutang potently inhibited the secretion of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β in phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated human mast cells. However, IL-6 secretion was enhanced at the same conditions. Dodutang also inhibited the main inflammatory cytokine TNF-α protein expression in human mast cells. These results provide evidences that Dodutang may be beneficial in the treatment of acute and chronic allergic diseases.

Novel findings in inhibition of mast cell-dependent immediate-type cutaneous reactions by Gahmi-Shini-San

This report describes an inhibitory effect of Gahmi-Shini-San (GSS) on mast cell-mediated immediate-type allergic reactions. GSS is an Oriental herbal medication, which has been successfully used in Korea for the treatment of allergic disorders, mainly skin anaphylactic diseases. GSS inhibited the ear swelling response induced by intradermal injection of compound 48/80 in a mouse model on a concentration-dependent basis. The mast cells in mouse ear tissue were stained by alcian blue/nuclear fast red. GSS significantly inhibited the compound 48/80-induced degranulation from mast cells in ear tissue. GSS dose-dependently inhibited the histamine release from the rat peritoneal mast cells by compound 48/80. We also studied the effect of GSS on mast cell-dependent passive cutaneous anaphylaxis activated by dinitrophenyl IgE antibody. GSS showed inhibition of passive cutaneous anaphylaxis following oral administration. These results indicated that GSS has inhibitory effect on mast cell-dependent immediate type cutaneous reactions.

Fc(epsilon)Ri-dependent signaling pathways in human mast cells.

The aim of the present study is to investigate the anti-inflammatory and anti-allergic effects of taxifolin on mast cells and mast cell-mediated allergic reaction. We assessed the effect of taxifolin on the activation of bone marrow-derived mast cells (BMMCs) and rat basophilic leukemia (RBL)-2H3 cells induced by immunoglobulin E (IgE)/antigen (Ag), and the activation of human mast cell line (HMC-1) induced by PMA plus A23187. Taxifolin inhibited degranulation, generation of leukotriene C4 (LTC4), production of interlukin-6 (IL-6), and expression of cyclooxygenase-2 (COX-2) through blocking intracellular Ca2+ mobilization, phosphorylation of phospholipase Cγ (PLCγ) and mitogen-activated protein kinases (MAPKs), translocation of cytosolic phospholipase A2 (cPLA2) and 5-lipoxygenase (5-LO), and Akt/IKK/NF-κB pathway, in BMMC cells. Furthermore, taxifolin suppressed phosphorylation of Syk, but without effect on Fyn and Lyn. Taxifolin also inhibited activation of RBL-2H3 and HMC-1 cells via Akt/IKK/NF-κB and MAPKs/cPLA2 signal pathway. Treatment with taxifolin attenuated the mast cell-mediated passive cutaneous anaphylaxis (PCA) reaction. Our results suggest that taxifolin might become a potential drug candidate for the treatment of allergic and inflammatory diseases.

INHIBITORY EFFECTS OF MAST CELL-MEDIATED ALLERGIC REACTIONS BY CELL CULTURED SIBERIAN GINSENG

The crude drug “Siberian Ginseng (SG)” has long been used in empirical Oriental medicine for the nonspecific enhancement of resistance in humans and animals. In this study, we investigated the effect of cell cultured SG by oral administration in mast cell-mediated allergic reactions. SG dose-dependently inhibited compound 48/80-induced systemic allergy with doses of 10−2 to 1 g/kg 1 h before oral administration. Of special note, SG inhibited systemic allergy with the dose of 1 g/kg by 25%. SG (1 g/kg) also inhibited passive cutaneous allergic reaction by 51%. SG dose-dependently inhibited histamine release from rat peritoneal mast cells. When SG (0.01 mg/ml) was added, the secretion of tumor necrosis factor-α (TNF-α) and interleukin-6 in anti-dinitrophenyl (DNP) IgE antibody-stimulated mast cells was inhibited 39.5% and 23.3%, respectively. In addition, SG inhibited anti-DNP IgE antibody-stimulated TNF-α protein expression in mast cells. Our studies provide evidence that SG may be beneficial in the treatment of various types of allergic diseases.

Inhibitory Effect of Mast Cell-Mediated Immediate-Type Allergic Reactions by Sulfapyridine

We examined the effect of sulfapyridine on mast cell-mediated immediate-type allergic reactions. Sulfapyridine (1 and 10 μg/kg) significantly inhibited systemic allergic reaction induced by compound 48/80 in rats. Sulfapyridine (1 and 10 μg/kg) also inhibited significantly local mast cell-mediated immediate-type allergic reactions activated by anti-dinitrophenyl (DNP) IgE. Moreover, sulfapyridine inhibited histamine release dose-dependently in the rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. When sulfapyridine was added, the level of cAMP in RPMC, transiently and significantly increased about 4-fold compared with that of basal cells. These results indicate that sulfapyridine inhibits mast cell-mediated immediate-type allergic reactions in vivo and in vitro.

Inhibitory Effect of Mast Cell-Mediated Immediate-Type Allergic Reactions in Rats by Perilla Frutescens

We investigated the effect of aqueous extract of Perilla frutescens(Labiatae) (PFAE) on the mast cell-mediated immediate-type allergic reactions. PFAE(0.05 to 1 g/kg) dose-dependently inhibited systemic allergic reaction induced by compound 48/80 in rats. PFAE(0.1 and 1 g/kg) also significantly inhibited local allergic reaction activated by anti-DNP IgE. When PFAE was pretreated at the same concentrations with systemic allergic reaction test, the plasma histamine levels were reduced in a dose-dependent manner. PFAE(10−3 to 1 mg/ml) dose-dependently inhibited the histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. The level of cyclic AMP in RPMC, When PFAE(1 mg/ml) was added, transiently and significantly increased about 4-fold compared with that of basal cells. Moreover, PFAE(0.001 and 0.01 mg/ml) had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-α production. These results indicate that PFAE inhibits mast cell-mediated immediate-type allergic reactions in vivo and in vitro.

Targeting Janus Kinase 3 in Mast Cells Prevents Immediate Hypersensitivity Reactions and Anaphylaxis

Janus kinase 3 (JAK3), a member of the Janus family protein-tyrosine kinases, is expressed in mast cells, and its enzymatic activity is enhanced by IgE receptor/FcepsilonRI cross-linking. Selective inhibition of JAK3 in mast cells with 4-(4'-hydroxylphenyl)-amino-6, 7-dimethoxyquinazoline) (WHI-P131) blocked the phospholipase C activation, calcium mobilization, and activation of microtubule-associated protein kinase after lgE receptor/FcepsilonRI cross-linking. Treatment of IgE-sensitized rodent as well as human mast cells with WHI-P131 effectively inhibited the activation-associated morphological changes, degranulation, and proinflammatory mediator release after specific antigen challenge without affecting the functional integrity of the distal secretory machinery. In vivo administration of the JAK3 inhibitor WHI-P131 prevented mast cell degranulation and development of cutaneous as well as systemic fatal anaphylaxis in mice at nontoxic dose levels. Thus, JAK3 plays a pivotal role in IgE receptor/FcepsilonRI-mediated mast cell responses, and targeting JAK3 with a specific inhibitor, such as WHI-P131, may provide the basis for new and effective treatment as well as prevention programs for mast cell-mediated allergic reactions.

INHIBITORY EFFECT OF MAST CELL-MEDIATED IMMEDIATE-TYPE ALLERGIC REACTIONS BY CICHORIUM INTYBUS

We investigated the effect of an aqueous extract of Cichorium intybus (CIAE) on mast cell-mediated immediate type allergic reactions. CIAE (0.1–1000 mg kg−1) dose-dependently inhibited systemic anaphylactic reaction induced by compound 48/80 in mice. Especially, CIAE inhibited compound 48/80-induced anaphylactic reaction 100% with the dose of 1000 mg kg−1. CIAE 1000 mg kg−1also significantly inhibited local anaphylactic reaction activated by anti-dinitrophenyl (DNP) IgE. When mice were pretreated with CIAE at a concentration ranging from 0.1 to 1000 mg kg−1, the plasma histamine levels were reduced in a dose-dependent manner. CIAE (1–1000 μg ml−1) dose-dependently inhibited histamine release from the rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. The level of cAMP in RPMC, when CIAE (1000 μg ml−1) was added, increased significantly compared with that of control cells. These results indicate that CIAE inhibits mast cell-mediated immediate-type allergic reactions in vivo and in vitro .

Genetic and Biochemical Evidence for a Critical Role of Janus Kinase (JAK)-3 in Mast Cell-Mediated Type I Hypersensitivity Reactions

We investigated the role of JAK3 in IgE receptor/FcϵRI-mediated mast cell responses. IgE/antigen induced degranulation and mediator release were substantially reduced withJak3−/−mast cells from JAK3-null mice that were generated by targeted disruption ofJak3gene in embryonic stem cells. Further, treatment of mast cells with 3′bromo-4′-hydroxylphenyl)-amino-6,7-dimethoxyquinazoline (WHI-P154), a potent inhibitor of JAK3, inhibited degranulation and proinflammatory mediator release after IgE receptor/ FcϵRI crosslinking. Thus, JAK3 plays a pivotal role in IgE receptor/ FcϵRI-mediated mast cell responses and targeting JAK3 may provide the basis for new and effective treatment as well as prevention programs for mast cell-mediated allergic reactions.

Lavender oil inhibits immediate-type allergic reaction in mice and rats.

We studied the effects of lavender oil on mast cell-mediated immediate-type allergic reactions in mice and rats. Lavender oil (1:500, 1:100, 1:10, 1:1, 1:0) inhibited concentration-dependently mast cell-dependent ear swelling response induced by compound 48/80 in mice by both topical and intradermal application. Lavender oil (1:500, 1:100, 1:10, 1:1, 1:0) inhibited concentration-dependently passive cutaneous anaphylaxis induced by anti-dinitrophenyl (DNP) IgE in rats by both topical and intradermal application. Lavender oil (1:500, 1:100, 1:10, 1:1, 1:0) also inhibited concentration-dependently the histamine release from the peritoneal mast cells by compound 48/80 or anti-DNP IgE. Moreover, lavender oil (1:1000, 1:100, 1:10, 1:0) had a significant inhibitory effect on anti-DNP IgE-induced tumour necrosis factor-alpha secretion from peritoneal mast cells. These results indicate that lavender oil inhibits immediate-type allergic reactions by inhibition of mast cell degranulation in-vivo and in-vitro.

MAGNOLIAE FLOS INHIBITS MAST CELL-DEPENDENT IMMEDIATE-TYPE ALLERGIC REACTIONS

The mast cell plays a pivotal role in initiating allergic response by secreting intracytoplasmic granular mediators such as histamine. Magnoliae flos has been used for the treatment of allergic disease in Korea. However, its effect in experimental models remains unknown. The present report describes an inhibitory effect of Magnoliae flos on mast cell-mediated immediate-type allergic reactions. Topical application of compound 48/80 can induce an ear swelling response in normal (WBB6F1-+/+) mice but not in the congenic mast cell-deficient WBB6F1-W/Wvmice. Magnoliae flos inhibited concentration-dependently mast cell-dependent ear swelling response induced by compound 48/80 by topical application. Magnoliae flos inhibited concentration-dependently passive cutaneous anaphylaxis induced by anti-dinitrophenyl (DNP) IgE in rats by topical application. Magnoliae flos also inhibited concentration-dependently the histamine release from the rat peritoneal mast cells by compound 48/80 or anti-DNP IgE. Moreover, Magnoliae flos had a significant inhibitory effect on compound 48/80-induced systemic anaphylactic reaction. These results indicate that Magnoliae flos inhibits immediate-type allergic reactions by inhibition of mast cell degranulationin vivoandin vitro.

Shini-san inhibits mast cell-dependent immediate-type allergic reactions.

Shini-San has been used for treatment of allergic disease in Korea. However, its effect in experimental models remains unknown. The mast cell plays a pivotal role in initiating allergic response by secreting intracytoplasmic granular mediators such as histamine. The present report describes an inhibitory effect of Shini-San on mast cell-mediated immediate-type allergic reactions. Topical application of compound 48/80 can induce an ear swelling response in normal (WBB6F1(-)+/+) mice but not in congenic mast cell-deficient WBB6F1-W/WV mice. Shini-San inhibited concentration-dependent mast cell-dependent ear swelling response induced by compound 48/80 in normal mice. Shini-San inhibited concentration-dependent passive cutaneous anaphylaxis induced by anti-dinitrophenyl (DNP) immunoglobulin E (IgE) in rats by topical application. Shini-San also inhibited in concentration-dependent fashion the histamine release from the rat peritoneal mast cells by compound 48/80 or anti-DNP IgE. Moreover, Shini-San had a significant inhibitory effect on compound 48/80-induced systemic anaphylactic reaction. These results indicate that Shini-San inhibits immediate type allergic reactions by inhibition of mast cell degranulation in vivo and in vitro.

Short Communication Inhibition of immediate type allergic reactions by the aqueous extract of Kum-Hwang-San

We studied the effect of aqueous extract of Kum-Hwang-San (KHS) on mast cell-mediated immediate type allergic reactions. KHS (1–100 μg\\site) inhibited concentration-dependently mast cell-dependent ear swelling response induced by compound 48\\80 (200 μg\\site) in mice by both topical and intradermal application. KHS (0.1–100 μg\\site) inhibited concentration-dependently passive cutaneous anaphylaxis induced by anti-dinitrophenyl (DNP) IgE in rats by both topical and intradermal application. KHS also inhibited concentration-dependently the histamine release from the rat peritoneal mast cells (RPMC) by compound 48\\80 and anti-DNP IgE. Moreover, KHS had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor- fn2 fn2 tumor necrosis factor- α; HSA: human serum albumin; ELISA: enzyme linked immunosorbent assay. (TNF-α) secretion from RPMC. These results indicate that KHS inhibits immediate type allergic reactions by inhibition of histamine release and TNF-α secretion from mast cells in vivo and in vitro.

Inhibitory Effect of Mast Cell-Mediated Immediate-Type Allergic Reactions in Rats by Spirulina

We investigated the effect of spirulina on mast cell-mediated immediate-type allergic reactions. Spirulina dose-dependently inhibited the systemic allergic reaction induced by compound 48/80 in rats. Spirulina inhibited compound 48/80-induced allergic reaction 100% with doses of 100–1000 μg/g body weight, i.p. Spirulina (10–1000 μg/g body weight, i.p.) also significantly inhibited local allergic reaction activated by anti-dinitrophenyl (DNP) IgE. When rats were pretreated with spirulina at a concentration ranging from 0.01 to 1000 μg/g body weight, i.p., the serum histamine levels were reduced in a dose-dependent manner. Spirulina (0.001 to 10 μg/mL) dose-dependently inhibited histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. The level of cyclic AMP in RPMC, when spirulina (10 μg/mL) was added, transiently and significantly increased about 70-fold at 10 sec compared with that of control cells. Moreover, spirulina (10 μg/mL) had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-α production. These results indicate that spirulina inhibits mast cell-mediated immediate-type allergic reactions in vivo and in vitro.